Replication Data for: ‘Novel Human/Non-Human Primate Cross-Reactive Anti-Transferrin Receptor Nanobodies for Brain Delivery of Biologics‘
Description
This dataset contains raw data contributing to the publication ‘Novel Human/Non-Human Primate Cross-Reactive Anti-Transferrin Receptor Nanobodies for Brain Delivery of Biologics‘. This publication is about the discovery of nanobodies (variable domain of camelid heavy chain-only antibodies) binding both human and non-human primate transferrin receptor (TfR) that could serve as moieties to improve brain permeability of therapeutic antibodies. The blood-brain barrier (BBB), while being the gatekeeper of the central nervous system (CNS), is a bottleneck for the treatment of neurological diseases, as most of the biologicals do not reach their brain targets in sufficient quantities. Receptor-mediated transcytosis (RMT) is one physiological mechanism in which nutrients are recognized by specific receptors that are expressed on the surface of the endothelial cells, internalized in intracellular vesicles, and finally released in the brain parenchyma. Targeting such RMT receptors with antibodies or nanobodies is a strategy to increase the brain permeabilities of biologicals. Among these receptors, TfR is one of the most exploited RMT mechanisms for brain drug delivery. Here we report the discovery of two nanobodies that were able to bind human and cynomolgus TfRs, making these nanobodies more clinically relevant. Whereas nanobody BBB00515 bound cynomolgus TfR with 18 times more affinity than it did human TfR, nanobody BBB00533 bound human and cynomolgus TfR with similar affinities. When fused with an anti-beta-site amyloid precursor protein cleaving enzyme (BACE1) antibody (1A11AM), each of the nanobodies was able to increase its brain permeability after peripheral injection. A 40% reduction of brain Aβ1–40 levels could be observed in mice injected with anti-TfR/BACE1 bispecific antibodies when compared to vehicle-injected mice. In summary, we found two nanobodies that could bind both human and cynomolgus TfRs with the potential to be used clinically to increase the brain permeability of therapeutic biologicals.
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Tags
- bio-layer-interferometry
- nanobody
- elisa
- surface-plasmon-resonance
- flow-cytometry